Highly potent, non-basic 5-HT 6 ligands. Site mutagenesis evidence for a second binding mode at 5-HT 6 for antagonism

…, JM Brothers, M Ilnicka, SW Lee, T Mirzadegan

Index: Harris III, Ralph N.; Stabler, Russel S.; Repke, David B.; Kress, James M.; Walker, Keith A.; Martin, Renee S.; Brothers, Julie M.; Ilnicka, Mariola; Lee, Simon W.; Mirzadegan, Tara Bioorganic and Medicinal Chemistry Letters, 2010 , vol. 20, # 11 p. 3436 - 3440

Full Text: HTML

Citation Number: 14

Abstract

A series of 5-HT6 ligands derived from (R)-1-(amino) methyl-6-(phenyl) sulfonyltetralin was prepared that yielded several non-basic analogs having sub-nanomolar affinity. Ligand structure–activity relationships, receptor point mutation studies, and molecular modeling of these novel ligands all combined to reveal a new alternative binding mode to 5-HT6 for antagonism.